We propose to study the repair of articular cartilage defects which have been filled with committed chondrocytes or mesenchymal stem cells. Committed chondrocytes will be isolated, expanded in supportive tissue culture environments, and implanted with satisfactory delivery vehicles in vivo repair sites. Mesenchymal stem cells will be identified, isolated, and expanded. Techniques will be developed to isolate mesenchymal stem cells from the bone marrow and periosteum of adult donors and to drive these cells towards chondrocytic phenotype. Specific delivery vehicles will be developed to immobilize cells in specific in vivo sites. Cell surface markers will be utilized to identify these cells and to follow their phenotypic differentiation and reparative integration into cartilage. The regeneration of articular cartilage will be evaluated by quantitative histology, immunohistochemistry, biomechanical and biochemistry parameters. The immunogeneicity of the implants will be evaluated by a mixed implant cell-leukocyte culture. The local host response will be measured by testing synovial fluid for implant-specific antibody in a microcytotoxicity test. The long-term goal of this proposal is to develop practical clinical methodologies which utilize autologous cell-based technologies in the regeneration of cartilagenous defects.